Modulation of cholinergic neurotransmission in guinea-pig airways by opioids. |
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| Authors: | M. G. Belvisi C. D. Stretton P. J. Barnes |
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| Affiliation: | Department of Thoracic Medicine, National Heart and Lung Institute, London. |
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| Abstract: | 1. Opioid receptors have been localised on sensory fibres in the vagus nerve and opioids have previously been shown to inhibit non-adrenergic, non-cholinergic (NANC) neurotransmission in guinea-pig bronchi in vitro and in vivo. We have now investigated whether an inhibitory effect could be demonstrated on cholinergic neurotransmission. 2. Electrical field stimulation (EFS) (8 Hz, 0.5 ms, 40 V for 20 s) produced only a rapid, cholinergic response in the upper trachea but in the lower trachea and main bronchi a cholinergic response which was atropine-sensitive and a longer lasting NANC contraction that was atropine-insensitive was demonstrated. This slow contraction could be blocked by tetrodotoxin and capsaicin pretreatment. 3. [D-Ala2, NMePhe4, Gly-ol5]enkephalin (DAMGO), a selective mu-opioid receptor agonist, inhibited the cholinergic response to EFS at 8 Hz in a dose-dependent manner in main bronchi (IC50 = 113 nM with a maximal inhibition of 35.7 +/- 5.6% 10 microM, n = 5). In the lower trachea, DAMGO inhibited the cholinergic response to a similar extent (inhibition of 35.8 +/- 3.5% at 10 microM, n = 5). However, DAMGO had no effect on the contractile response to exogenously applied acetylcholine in the main bronchi. By contrast, opioids had no inhibitory effect on cholinergic neurotransmission in the upper trachea. DAMGO (1 microM) inhibited the cholinergic response to EFS in a frequency-dependent manner in the main bronchi with greater inhibition at lower frequencies of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) |
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